The long-term goal of this work is the understanding of the regulation of tyrosine hydroxylase in the central nervous system. Towards this end, we have studied the activation of the enzyme (via a decrease in cofactor Km with phosphorylation and G-75 chromatography as well as the reported activation with EGTA and calcium. We have been unable to verify these reports. We have further found that there appears to be a relationship between activation via phosphorylation and catecholamine concentration. Further studies will focus on G-75 activation, dopamine Ki values under several conditions, and experiments designed towards the elucidation of a mechanism of activation common to all of the activating procedures.